Meso-substituted porphyrins

ABSTRACT

Meso-substituted porphyrins of general formula (I) suitable for the use as photosensitizing agents, in particular in photodynamic therapy, are herein described.

FIELD OF THE INVENTION

The present invention refers to meso-substituted porphyrins of formula(I) hereinafter reported, the processes related to their preparation anduse as photosensitising agents for therapeutic, diagnostic andphotosterilisation uses.

STATE OF THE ART

It is known that tetrapyrrolic macrocycles, like porphyrins or otherphotosensitisers, are able to preferentially localise in neoplastictissues and, once photo-activated by irradiation with visible light,they are capable of generating hyper-reactive derivatives of oxygen suchas radicals and singlet-oxygen. Due to their high intrinsic reactivity,these species trigger irreversible oxidative cytotoxyc processes againstcells and tissues, thus being highly cytotoxic after the localisation ofthe photosensitiser onto targets and irradiation.

Thanks to their properties, porphyrins are used as photosensitizers forthe treatment of tumours in the so-called “photodynamic therapy”(hereinafter referred to as PDT).

A typical PDT protocol is based on the administration of an appropriatedose of photosensitizer, followed by irradiation of the tissues whereinthe tumour is localised by using light of appropriate wavelength, thuscausing, by the so-called photodynamic effect, the preferential orselective elimination of the tumour mass. Due to the selectivelocalisation in tumour tissues these photosensitizers can therefore beused not only for therapeutic purposes, but also as diagnostic agents astheir high fluorescence quantum yield allow the direct visualisation ofthe tumour lesion.

Besides in the photoinactivation of tumour cells, it has been shown thatphotosensitizers can also be used in the treatment and diagnosis ofpre-tumour pathologies and for various hyperproliferative diseases likepsoriasis, actinic keratosis, atheromas, endoarterial hyperplasia andprostate hyperplasia, as well as for microbial photoinactivation andtherefore in the treatment of bacterial and micotic infections.

Although the early use of phorphyrins in PDT has given encouragingresults, the compounds prepared until now need further improvementsbecause of their markedly limited efficiency and poor selectivity towardthe eukaryotic cells and/or micro-organisms, and because of theprolonged persistence in the skin, which often may cause phenomena ofgeneralised photosensitivity (Jori G., J. Photochem. Photobiol., B:Biol., Vol. 36, pp. 87-93, 1996).

Thus it is evident how important it is to develop novel porphyrincompounds suitable for the use as therapeutic agents in PDT and asdiagnostic agents, but not showing the limitations illustrated above.

Porphyrin derivatives bearing cationic groups have been previouslydescribed (Merchat et al. J. Photochem. Photobiol. 32, 153-157, 1996;Merchat et al. J. Photochem. Photobiol. 35, 149-157, 1996) and assessedfor their photodynamic properties in the bacteria photoinactivation.These compounds bear trimethyl-anilinium groups or quaternary ammoniumpyridinium groups in the meso-positions and therefore are endowed by ahydrophilic nature.

Other photosensitisers such as phthalocyanines having hydrophilic and/oramphiphilic characteristics are known; for example, the InternationalApplications No. WO 01/96343 and WO 02/090361, and in the U.S. Pat. No.5,965,598, all in the name of the Applicant, disclose various evenlysubstituted hydrophilic phthalocyanines, as well as noncentrosymmetrical phthalocyanines bearing cationic or protonable groupon the macrocycle.

SUMMARY OF THE INVENTION

The Applicant has now found a novel series of photosensitizers havingparticularly advantageous properties compared to the known compounds.

These novel compounds have shown optimum physical-chemical features fortherapeutic applications, particularly in relation to their absorptionin the region of the visible spectrum, high molar extinctioncoefficients, high quantum yield in singlet oxygen production, that isexpressed by the photoinactivation of eukaryotic and prokaryotic cells.

The photosensitizers described by this invention are able to producesinglet oxygen by using various light sources and wavelengths. Inparticular they can be activated by visible red light radiation when thetreatment of deep seated tumours on infections is required as well as byblue visible radiation or white light radiations when is preferable totreat by means of the photodynamic process more superficial lesions suchas in the treatment of psoriasis, actinic keratoses, basal cellcarcinomas and other cancerous and pre-cancerous lesions of the skin andmucosas. Of particularly interest is the possibility to modulate theactivity of these products by acting on the radiation wavelength usedfor the activation. In fact it is well known that porphyrins are able toabsorb light in the red region and in the blue region of the visiblespectrum to a different extent. The combination of the light sourcedevised to these purposes and the differential absorption by theporphyrins, allows a unique possibility in order to precisely define theactivity of these compounds while used as photosensitizers in thephotodynamic treatment of the above mentioned pathologies.

The present compounds are therefore suitable for the photodynamictreatment of pathologies characterised by cellular hyperproliferationand for the photodynamic treatment of infections caused by pathogenicmicro-organisms, however can be also used as in vivo diagnostic agentsdue to the fluorescence released after excitation at various wavelengthin the visible region of the light spectrum. Finally these derivativescan be used as sterilising agents in the in vivo treatment such as thetreatment of wounds as well as in vitro treatments such as the blood orblood derivatives sterilisation.

Subject of the present invention are therefore the porphyrins of generalformula (I)

wherein

R is the following group of formula (II)

wherein

X is selected from the group consisting of O, S, CH₂, COO, CH₂CO,O(CH₂)₂O, O(CH₂)₃O and N;

Z is selected from between N and CH₂N;

Y is selected from aliphatic groups, linear or branched, saturated orunsaturated, having from 1 to 10 carbon atoms, and phenyl, possiblysubstituted, or Y forms with Z a saturated or unsaturated heterocycle,possibly substituted, comprising up to two heteroatoms selected from thegroup consisting of N, O and S;

R₄ and R₅, equal or different from each other, are selected from H andalkyl groups having from 1 to 3 carbon atoms, or they form with the Zgroup a saturated or unsaturated heterocycle, possibly substituted,comprising up to two heteroatoms selected from the group consisting ofN, O and S;

R₆ is selected from H and aliphatic groups, linear or branched,saturated or unsaturated, having from 1 to 5 carbon atoms, possiblysubstituted with alkylamine or alkylammonium groups having alkyl chainscomprising from 1 to 5 carbon atoms, or forming a saturated heterocyclecomprising up to two heteroatoms selected from between O and N;

d, m, and n, equal of different from each other, are selected from 0 and1;

v and s, equal or different from each other, are integers comprisedbetween 1 and 3;

R₁ is selected from H and a group of formula (III)

wherein

G is selected from H and P—(CH₂)₁—(W)_(f)-J, wherein

P is selected from the group consisting of O, CH₂, CO₂, NHCONH and CONH;

I is an integer comprised between 0 and 5;

W is selected from the group consisting of O, CO₂, CONH and NHCONH;

f is selected from between 0 and 1;

J is H or an alkyl group (CH₂)_(q)—CH₃, wherein q is an integercomprised between 0 and 20;

R₂ and R₃, equal or different from each other, are selected from betweenR and R₁, wherein R and R₁ are defined as above,

M is chosen from 2H and a metal selected from the group consisting ofZn, Mg, Pt, Pd, Si(OR₇)₂, Ge(OR₇)₂ and AlOR₇, wherein R₇ is chosen frombetween H and C1-C15 alkyl,

and pharmaceutically acceptable salts thereof.

Further subject of the present invention are the processes for thepreparation of the above said compounds of formula (I), the novelintermediates in these processes and the conjugates in which thecompounds of formula (I) are site specifically conjugated withbio-organic carriers, such as aminoacids, polypeptides, proteins andpolysaccharides.

The present compounds of formula (I), as well as the correspondingconjugates, are useful for the treatment of microbial infections(bacterial, fungal and viral), in the photodynamic treatment of tumour,pre-cancerous pathologies, and other hyperproliferative diseases.

The present compounds (I) and the corresponding conjugates are useful aswell, as diagnostic agents for the identification of pathologicallyaffected areas and for photodynamic sterilization of blood and bloodderivatives.

Features and advantages of the present compounds of formula (I) will beillustrated in details in the following description.

DETAILED DESCRIPTION OF THE INVENTION

By “saturated or unsaturated heterocycle possibly substituted” accordingto the invention, an heterocycle is preferably meant, which is selectedfrom the group consisting of morpholine, piperidine, pyridine,pyrimidine, piperazine, pyrrolidine, pyrroline, imidazole, aniline andjulolidine (2,3,6,7-tetrahydro-1H,5H pirido[3,2,1-Ij]quinoline).

According to a particular embodiment of the invention, the presentporphyrins of formula (I) have two or three groups with amino orammonium substituents in two or three of the four meso-positions, and Hor groups with non polar substituents on the other meso-positions.

Preferred compounds according to the invention are those wherein thegroup R comprises substituents bearing tertiary or quaternary nitrogen;more preferred are the present compounds of formula (I) wherein thegroup is selected from the group consisting of:

Pharmaceutically acceptable salts of porphyrins of general formula (I)according to the invention, bearing basic substituents, includeconventional acid addition salts, obtained by the addition of HCl,H₃PO₄, H₂SO₄, HBr or by ion-exchange. Additionally, salts obtained byreaction of a carboxylic function or acid groups with the porphyrin ringare within the scope of the present invention.

The present compounds of formula (I) show valuable photodynamiccharacteristics making them useful in photodynamic therapy (PDT) againstbacterial, fungal, and viral infections, for various hyperproliferativediseases, as well as for photosterilization of blood and bloodderivatives, such as platelets and erythrocytes. In this particular casethe present compounds can be added to blood or blood derivatives as suchor bound to suitable matrix, according to the known techniques, andthereafter irradiated. Moreover they can be used as diagnostic agentsfor the identification of pathologically affected areas.

The present products possess a high molar absorption coefficient, whichrepresents an important requirement for an effective therapeuticresponse.

They may be activated by tissue penetrating radiation having awavelength around 650 nm, and hence they are suitable for the use in PDTagainst diseases, both dermatological and internal, but they also can beactivated by using less tissue penetrating light for the photodynamictreatment of very superficial lesion, especially when a little damage ofthe skin should be accomplished or, for instance, when a fluorescenceemission from the tissue is preferred such as in the photodiagnosticprocedures of the above mentioned pathologies.

The products formed by photobleaching of the present compounds are nontoxic. This finding reinforces their usefulness as therapeutic since,after having exploited their action, the compounds are inactivated bythe light and then are no more potentially toxic in vivo.

The present compounds are active in the singlet oxygen production orallow the production of reactive species of oxygen under conditions ofpoor oxygenation. Such requirement is particularly important because itallows to treat specifically anaerobic micro-organisms or tumour cells,well-known characterised by an environment poor of oxygen.

In particular, the present compounds possess very high efficiency formicro-organisms such as yeasts, fungi and mycoplasma, Gram-positive andGram-negative bacteria, and show a great ability in specificallylocalising on micro-organisms compared to the mammalian host cells.

The present invention comprises also the above described formula (I)compounds site-specifically conjugated with a bio-organic carrier ableto direct to a definite target.

According to the invention the carrier is usually chosen among moleculeshaving well-known specific binding capacities, for example aminoacids(preferably basic aminoacids), polypeptides (preferably consisting ofbasic aminoacids), proteins and polysaccharides normally used fortargeting purposes.

The binding porphyrin/carrier may occur for example between thecorresponding amino or carboxyl groups, or may occur involving otherspecific functional groups on the porphyrin moiety or on the carriermolecule.

Functional groups such as thiol, maleimide derivatives, α-bromo estersand amides, diazonium salts and azido derivatives can be introducedaccording to known procedures in order to pre-functionalise both theporphyrin or the carrier depending upon the selected carrier itself andits stability.

The compounds of the present invention can be prepared according toprocesses known in organic chemistry starting from suitable reagents.For example, when compounds of formula (I) in which R═R₂═R₃ are desired,they can be prepared according to a process selected from the groupconsisting of:

-   -   process comprising pre-functionalization of suitable reagents        with amino groups, followed by statistical synthesis of the        porphyrin ring, possible modification of the amino groups in        ammonium groups, and possible complexation with the metal cation        if the metal complex is required;    -   process comprising statistical synthesis with formation of the        porphyrin ring followed by functionalization of the porphyrin        with the present amino or ammonium groups, and possible        complexation with the metal cation; and    -   process comprising synthesis of the porphyrin ring through        suitable dipyrromethane derivatives followed by        functionalisation of the porphyrin with the present amino or        ammonium groups, and possible complexation with the metal        cation.

When compounds of formula (I) are desired in which R═R₂ and R₁═R₃, theycan be prepared for example according to a process comprising thesynthesis of the porphyrin ring through dipyrromethane followed byfunctionalisation of the porphyrin with aliphatic or aromatic amino orammonium groups, and possible complexation with the metal cation if themetal complex is required.

Some examples of the above said processes are illustrated in thefollowing schemes.

SCHEME 1: Synthesis of compounds of formula (I) in which R═R₂═R₃

The so-obtained porphyrin derivatives can be further processed to obtainthe present compounds of formula (I) for example according to the lastthree steps in the above Scheme 1B.

SCHEME 2: Synthesis of compounds in which R═R₂ and R₁═R₃

The present porphyrins can be converted in the corresponding metalcomplexes by treatment with the suitable metal cation according towell-known procedures in organic chemistry. The introduction of themetal cation into the porphyrin ring may be achieved before or after thefunctionalisation of the porphyrin ring with the present amino orammonium groups.

All the quaternary ammonium porphyrin iodides derivatives prepared canbe easily converted in the corresponding chlorides or other moreacceptable salts for biological purposes.

The compounds of the present invention have been prepared according tothe procedure described above, identified and characterised byspectroscopic (¹H-NMR, ¹³C-NMR), spectrophotometric (UV-Vis), andspectrometric (EI, ESI or DCI-MS) analytical techniques.

The following examples are given to provide a non limiting illustrationof the invention.

Example 1 Synthesis of5,10,15-tris-[4-(2-N,N,N-trimethylammoniumethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrintriiodide by Statistical Synthesis with Pre-Functionalization Step a)Synthesis of N,N-dimethyl-2-methylsulphonylethylamine

To a solution of N,N-dimethylethanolamine (890 mg, 10 mmol) andtriethylamine (1520 mg, 15 mmol) in anhydrous CH₂Cl₂, kept undernitrogen atmosphere, at 0° C., methansulphonyl chloride (1220 mg, 11mmol) was added. The mixture was kept under stirring and at 0° C. for 1hour, and then concentrated by evaporation. The residue was dissolved inCH₂Cl₂, washed with Na₂CO₃ saturated solution and with deionized water.The organic phase was dried under Na₂SO₄ and the solvent removed byevaporation. The product was used as obtained, without purification, forthe following step b) (1330 mg, yield 80%).

¹H-NMR: (300 MHz, DMSO-d⁶) 3.51 (2H, t, J=5.8 Hz), 3.03 (6H, s), 3.00(2H, t, J=5.8 Hz), 2.71 (6H, s)

EI-MS: 167.23 Th [C₅H₁₃NO₃S]⁺

Step b) Synthesis of 4-(N,N-dimethylaminoethoxy)benzaldehyde

To a solution of 4-hydroxybenzaldehyde (500 mg, 4 mmol) and K₂CO₃ (662mg, 4.8 mmol) in anhydrous DMF, N,N-dimethyl-2-metilsulphonilethylamine(775 mg, 4.4 mmol) was added. The reaction mixture was heated to reflux,under magnetic stirring, for 4 hours, then poured in water to obtain asuspension from which the solid was isolated by filtration. The crudeproduct was purified by chromatography on silica gel (ethyl acetate), togive 379 mg of pure product of the title (yield 49%).

¹H-NMR: (300 MHz, DMSO-d⁶): 9.86 (1H, s), 8.78 (2H, d, J=8.8 Hz), 6.98(2H, d, J=8.8 Hz), 3.28 (2H, t, 5.5 Hz), 2.97 (2H, t, J=5.5 Hz), 2.71(6H, s)

EI-MS: 193.25 Th [C₁₁H₁₅NO₂]⁺

Step c) Synthesis of 4-decyloxybenzaldehyde

To a solution of 4-hydroxybenzaldehyde (732 mg, 6 mmol) in anhydrous DMF(13 ml), under nitrogen atmosphere, K₂CO₃ (1658 mg, 12 mmol), and, after10 minutes, iododecane (1785 mg, 7.2 mmol) were added. The mixture washeated to reflux for 3 hours, then water was added and the product wasextracted with CH₂Cl₂. The organic layers were washed with water andwith NaCl saturated solution, dried with Na₂SO₄. After evaporation ofthe solvent, the crude product was purified by chromatography on silicagel (Petroleum ether/Ethyl acetate 11/1) and 1530 mg (yield 97%) of thepure product of the title were obtained.

¹H NMR (300 MHz, DMSO-d⁶): 9.84 (1H, s), 7.82 (2H, d, J=9 Hz), 7.09 (2H,d, J=9 Hz), 4.06 (2H, t, J=6.6 Hz), 1.71 (2H, tt, J=6.6 Hz, 6.5 Hz),1.30 (14H, m), 0.83 (3H, t, 6.5 Hz).

¹³C NMR (75 MHz, DMSO-d⁶): 191.7, 164.2, 132.2, 130.0, 115.3, 68.4,31.7, 29.4, 29.4, 29.2, 29.1, 28.9, 25.8, 22.5, 14.3.

EI-MS: 262.3 Th [C₁₇H₂₆O₂]⁺

Step d) Synthesis of5,10,15-tris-[4-(2-N,N-dimethylaminoethoxy)phenyl]-[20-(4-decyloxy)phenyl]porphyrin

To a solution of 4-decyloxybenzaldehyde coming from step c) (505 mg, 2mmol), 4-(N,N-dimethylaminoethoxy)benzaldehyde prepared as described instep b) (1160 mg, 6 mmol) and pyrrole (537 mg, 8 mmol) in anhydrousCH₂Cl₂, trifluoroacetic acid (570 mg, 6.7 mmol) was added and themixture was kept under magnetic stirring, at room temperature, undernitrogen atmosphere, for 20 hours. Then p-chloranil (1650 mg, 6.7 mmol)was added and the final mixture stirred for additional 4 hours. Work-up:washing with Na₂CO₃ saturated solution, drying on Na₂SO₄, and removingsolvent by evaporation. The crude product was finally purified byreverse phase chromatography on C18 silica gel (water/acetonitrile 3/1),to give 245 mg of the title product (yield 12%).

¹H NMR (300 MHz, CDCl₃): 8.85 (8H, m), 8.11 (8H, m), 7.29 (8H, m), 4.40(6H, t, J=5.6 Hz), 4.25 (2H, t, J=6.3 Hz), 2.99 (6H, t, J=5.6 Hz), 2.53(18H, s), 1.97 (2H, tt, J=7.2 Hz), 1.65-1.32 (14H, m), 0.91 (3H, t,J=6.6 Hz); −2.77 (2H, s).

¹³C NMR (75 MHz, CDCl₃, selected data): 163.4, 163.0, 161.8, 135.6,131.1, 118.0, 112.7, 77.2, 68.3, 66.8, 58.1, 49.1, 44.4, 37.7, 31.9,29.6, 29.4, 29.3, 26.2, 22.6, 14.0.

ESI-MS: m/z 1032.5 Th [C₆₆H₇₈N₇O₄]⁺.

Step e) Synthesis of5,10,15-tris-[4-(2-N,N-dimethylaminoethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrinatezinc (II)

To a solution of5,10,15-tris-4-(2-N,N-dimethylaminoethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrincoming from step d) (40 mg, 0.04 mmol) in CHCl₃, ZnOAc₂ (3.7 mg, 0.02mmol) was added. The reaction mixture was kept under magnetic stirring,at room temperature, for 30 minutes, then filtered in vacuum and theliquid phase concentrated by evaporation to give 34.7 mg of the desiredproduct of the title (yield 80%).

¹H-NMR: (300 MHz, DMSO-d⁶): 8.92-8.77 (6H, m), 8.81-8.68 (2H, m),8.23-8.17 (6H, m), 8.10 (2H, d, J=8.7 Hz), 7.84 (2H, d, J=8.7 Hz)7.90-7.81 (6H, m), 3.66 (2H, m), 3.40 (2H, t, J=5.8 Hz), 2.95 (2H, t,J=5.5 Hz), 2.68 (6H, s), 2.01-0.080 (9H, m)

ESI-MS: 1094.5 Th [C₆₆H₇₆N₇O₄Zn]⁺

Step f) Synthesis of5,10,15-tris-[4-(2-N,N,N-trimethylammoniumethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrinatezinc (II) triiodide

To a solution of5,10,15-tris-[4-(2-N,N-dimethylaminoethoxy)-phenyl]-20-[(4-decyloxy)phenyl]porphyrinatezinc (II) coming from step e) (20 mg, 0.02 mmol) in dry NMP, iodomethane(0.6 mmol) was added. The reaction mixture was kept under magneticstirring, at room temperature, for 8 hours, and then diethyl ether wasadded slowly until a precipitate appeared. The suspension was filteredand the solid re-crystallised from CHCl₃/diethyl ether to give 22.9 mgof pure product of the title (yield 75%).

¹H-NMR: (300 MHz, DMSO-d⁶): 8.90-8.72 (6H, m), 8.81-8.65 (2H, m),8.26-8.12 (6H, m), 8.15 (2H, d, J=8.7 Hz), 7.84 (2H, d, J=8.7 Hz)7.80-7.74 (6H, m), 3.66 (2H, m), 4.30 (2H, t, J=5.6 Hz), 2.95 (2H, t,J=5.5 Hz), 3.43 (6H, s), 2.07-0.75 (9H, bm)

ESI-MS: m/z 379.5 Th [C₆₉H₈₄N₇O₄Zn]³⁺

Step g) Synthesis of5,10,15-tris-[4-(2-N,N,N-trimethylammoniumethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrintriiodide

To a solution in CHCl₃ of5,10,15-tris-[4-(2-N,N,N-trimethylammoniumethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrinatezinc (II) triiodide coming from step f) (30 mg, 0.02 mmol) TFA wasadded. The mixture was kept at room temperature for 20 minutes, thenfiltered through K₂CO₃, and the solvent remove by evaporation, to give26.3 mg of product of the title (yield 90%).

¹H NMR (300 MHz, CD3OD): 8.86 (8H, m), 8.49 (8H, m), 7.69 (6H, m), 7.57(2H, m), 4.91 (6H, m), 4.35 (2H, t, J=6 Hz), 4.11 (6H, m), 3.46 (27H,s), 2.00 (2H, m), 1.67 (2H, J=6 Hz), 1.56-1.28 (12H, m), 0.92 (3H, t,J=6.6 Hz).

¹³C NMR (75 MHz, CD₃OD, selected data): 149.5, 140.3, 134.7, 130.0,114.4, 112.7, 98.8, 68.4, 65.5, 62.5, 53.8, 31.9, 29.6, 29.5, 29.4,29.3, 26.1, 22.5, 13.2.

ESI-MS: m/z 358.8 Th [C₆₉H₈₆N₇O₄]³⁺.

Example 2 Synthesis of5,10,15-tris-[4-(2-N,N-trimethylammoniumethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrintriiodide by Statistical Synthesis with Functionalization on thePorphyrin Step a) Synthesis of 4-(2-hydroxyethoxy)benzaldehyde

To a solution of 4-hydroxybenzaldehyde (366 mg, 3 mmol) in anhydrous DMF(7 ml), under nitrogen atmosphere, K₂CO₃ (829 mg, 6 mmol), and, after 10minutes, bromoethanol (450 mg, 3.6 mmol) were added. The mixture washeated to reflux for 3 hours, then water was added and the product wasextracted with CH₂Cl₂. The organic layers were washed with water andwith NaCl saturated solution, dried with Na₂SO₄. After evaporation ofthe solvent, the crude product was purified by chromatography on silicagel (Petroleum ether/Ethyl acetate 2/1); 400 mg (yield 80%) of pureproduct of the title were obtained.

¹H NMR (300 MHz, DMSO-d⁶): 9.85 (1H, s), 7.84 (2H, d, J=8.7 Hz), 7.12(2H, d, J=8.7 Hz), 4.87 (1H, t, J=5.1 Hz), 4.10 (2H, dt, J=5.1 Hz, 4.8Hz), 3.73 (1H, t, J=4.8 Hz).

¹³C NMR (75 MHz, DMSO-d⁶): 191.7, 164.2, 132.2, 130.0, 115.4, 70.5,59.8.

Step b) Synthesis of5,10,15-tris-[4-(2-hydroxyethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrin

To a solution of 4-decyloxybenzaldehyde (190 mg, 0.72 mmol),4-(2-hydroxyethoxy)benzaldehyde (360 mg, 2.17 mmol) and pyrrole (241 mg,3.6 mmol) in dry CH₂Cl₂, trifluoroacetic acid (228 mg, 2 mmol) was addedand the mixture was kept under magnetic stirring, at room temperature,under nitrogen atmosphere, for 4 hours. Then p-chloranil (492 mg, 2mmol) was added and the final mixture stirred for additional 15 hours,then the organic phase was washed with Na₂CO₃ saturated solution, driedon Na₂SO₄ and the solvent removed by evaporation. The crude product waspurified by chromatography on silica gel (THF/petroleum ether 1/1+1%TEA, to THF+1% TEA), to give 75 mg of the title product (yield 10%).

¹H NMR (300 MHz, CDCl₃): 8.87 (8H, m), 8.10 (8H, m), 7.27 (8H, m), 4.37(6H, t, J=4.2 Hz), 4.21 (3H, m), 4.15 (8H, m); 1.96 (2H, tt, J=7.5 Hz),1.57-1.25 (14H, m), 0.90 (3H, t, J=6.9 Hz); −2.76 (2H, s).

¹³C NMR (75 MHz, CDCl₃, selected data): 159.0, 158.4, 135.6, 135.1,134.3, 131.0, 120.0, 119.6, 112.7, 77.2, 69.4, 68.3, 61.6, 31.9, 29.6,29.6, 29.5, 29.4, 29.3, 26.2, 22.6, 14.1.

ESI-Ms: m/z 951.2 Th [C₆₀H₆₃N₄O₇]⁺.

Step c) Synthesis of5,10,15-tris-[4-(2-methylsulphonylethoxy)phenyl]-20-(4-decyloxy)phenyl]porphyrin

To a solution of5,10,15-tris-[4-(2-hydroxyethoxy)phenyl]-20-(4-decyloxy)phenyl]porphyrin(70 mg, 0.073 mmol) in anhydrous CH₂Cl₂, under nitrogen atmosphere, at0° C., triethylamine (73 mg, 0.73 mmol) and methansulphonyl chloride (42mg, 0.37 mmol) were added. The mixture was kept under magnetic stirringat room temperature for 3 hours, then washed with NaHCO₃ saturatedsolution and with water. The organic phase was dried with Na₂SO₄ and thesolvent removed by evaporation. The crude product was purified bychromatography on silica gel (CH₂Cl₂/MeOH 50/1), to obtain 65 mg of thetitle product (yield 65%).

¹H NMR (300 MHz, CDCl₃): 8.87 (8H, m), 8.12 (8H, m), 7.29 (8H, m), 4.77(6H, t, J=4.5 Hz), 4.54 (6H, t, J=4.5 Hz), 4.25 (2H, t, J=6 Hz), 3.24(9H, s), 1.96 (2H, tt, J=8 Hz), 1.61-1.25 (14H, m), 0.91 (3H, t, J=7Hz); −2.77 (2H, s).

¹³C NMR (75 MHz, CDCl₃, selected data): 159.0, 157.8, 140.3, 135.6,135.6, 134.2, 130.9, 120.2, 119.4, 114.5, 112.8, 77.2, 68.3, 66.2, 66.1,37.9, 31.9, 29.6, 29.6, 29.5, 29.3, 26.2, 22.6, 14.1.

ESI-Ms: m/z 1185.1 Th [C₆₃H₆₉N₄O₁₃S₃]⁺.

Step d) Synthesis of5,10,15-tris-[4-(2-N,N-dimethylaminoethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrin

To a solution of5,10,15-tris-[4-(2-methylsulphonylethoxy)phenyl]-20-(4-decyloxy)phenyl]porphyrin(65 mg, 0.055 mmol) in anhydrous DMF (5 ml), under nitrogen atmosphere,K₂CO₃ (46 mg, 0.33 mmol), and, after 10 minutes, dimethylaminehydrochloride (27 mg, 0.055 mmol) were added. The mixture was heated at80° C. for 20 hours, then water was added and the product was extractedwith CH₂Cl₂. The organic layers were washed with water and with NaClsaturated solution, then dried with Na₂SO₄. After evaporation the crudeproduct was purified by chromatography on silica gel (THF to THF/DMF4/1). After the chromatography, the product was re-crystallized fromCHCl₃/Petroleum Ether 1/1 and 26 mg (yield 50%) of the title productwere obtained.

¹H NMR (300 MHz, CDCl₃): 8.85 (8H, m), 8.11 (8H, m), 7.29 (8H, m), 4.40(6H, t, J=5.6 Hz), 4.25 (2H, t, J=6.3 Hz), 2.99 (6H, t, J=5.6 Hz), 2.53(18H, s), 1.97 tt, J=7.2 Hz), 1.65-1.32 (14H, m), 0.91 (3H, t, J=6.6Hz); −2.77 (2H, s).

¹³C NMR (75 MHz, CDCl₃, selected data): 163.4, 163.0, 161.8, 135.6,131.1, 118.0, 112.7, 77.2, 68.3, 66.8, 58.1, 49.1, 44.4, 37.7, 31.9,29.6, 29.4, 29.3, 26.2, 22.6, 14.0.

UV-VIS (DMF): λ_(max) 651, 555, 518,430, 408, 264, 245, 235.

ESI-MS: m/z 1032.5 Th [C₆₆H₇₈N₇O₄]⁺.

Step e) Synthesis of5,10,15-tris-[4-(2-N,N,N-trimethylammonium)ethoxyphenyl]-20-[(4-decyloxy)phenyl]porphyrintriiodide

To a solution of5,10,15-tris-[4-(2-N,N-dimethylaminoethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrin(15 mg, 0.015 mmol) in dry NMP (5 ml), iodomethane (100 mg, 0.6 mmol)was added. The reaction mixture was kept under magnetic stirring, atroom temperature, for 20 hours, then diethyl ether was added slowlyuntil a precipitate appeared. The suspension was filtered and the solidcrystallized from MeOH/diethyl ether to give 20 mg of pure product ofthe title (yield 94%).

¹H NMR (300 MHz, DMSO-d⁶): 8.16 (6H, m), 8.08 (2H, m), 7.45 (6H, m),7.35 (2H, m), 4.76 (6H, m), 4.25 (2H, t, J=6 Hz), 3.97 (6H, m), 3.32(27H, s), 1.88 (2H, m), 1.56-1.28 (14H, m), 0.86 (3H, t, J=6.3 Hz);−2.91 (2H, s).

¹³C NMR (75 MHz, DMSO-d⁶, selected data): 158.0, 136.1, 134.9, 131.9,120.1, 113.9, 113.7, 68.3, 65.0, 62.55, 53.9, 31.9, 29.6, 29.5, 29.4,29.3, 26.2, 22.7, 14.5.

UV-VIS (DMF): λ_(max) 650, 554, 517, 431, 400, 254, 245, 234.

ESI-MS: m/z 358.8 Th [C₆₉H₈₆N₇O₄]³⁺.

Step b1) Synthesis of 2-[4-(di-1H-pyrrol-2-ylmethyl)phenoxy]ethanol

To a solution of 4-(2-hydroxyethoxy)benzaldehyde (664 mg, 4 mmol) inpyrrole (12.5 ml, 180 mmol), TFA (114 mg, 1 mmol) was added. Thereaction mixture was kept under magnetic stirring, at room temperature,for 1 hour, then ethyl acetate (200 ml) was added and the solutionwashed with NaHCO₃ saturated solution, then the organic phase was driedwith Na₂SO₄. After evaporation, the crude product was purified bychromatography (Petroleum ether/Ethyl acetate 1/1). 811 mg (yield 72%)of the title product were obtained.

¹H NMR (300 MHz, CDCl₃): 7.94 (2H, bs), 7.13 (2H, m), 6.87 (2H, m), 6.69(2H, m), 6.15 (2H, m), 5.91 (2H, m), 5.91 (1H, s), 4.07 (2H, dt, J=9,4.5 Hz), 3.95 (2H, dt, J=9, 7.5 Hz).

¹³C NMR (75 MHz, CDCl₃): 157.6, 134.7, 132.7, 129.5, 117.1, 114.6,108.4, 107.0, 69.1, 61.4, 43.1.

Step c1) Synthesis of5,10,15-tris-[4-(2-hydroxyethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrin

To a solution of 2-[4-(di-1H-pyrrol-2-ylmethyl)phenoxy]ethanol (620 mg,2.2 mmol, 4-decyloxybenzaldehyde (262 mg, 1 mmol) and4-(2-hydroxyethoxy)benzaldehyde (166 mg, 1.4 mmol) in dry CH₂Cl₂,trifluoroacetic acid (114 mg, 1 mmol) was added and the mixture was keptunder magnetic stirring, at room temperature, under nitrogen atmosphere,for 4 hours. Then p-chloranil (492 mg, 2 mmol) was added and the finalmixture stirred for additional 15 hours, then the organic phase waswashed with Na₂CO₃ saturated solution, dried on Na₂SO₄ and the solventremoved by evaporation. The crude product was purified by chromatographyon silica gel (THF/Petroleum ether 1/1+1% TEA, to THF+1% TEA), to give35 mg of title product (yield 3.7%).

According to the procedures described in Examples 1 or 2 the followingporphyrins have been prepared:

Example 35,10,15-tris-{[4-(N-methylpiperidin-4-yl)oxy]phenyl}20-[(4-decyloxy)phenyl]porphyrin

ESI-MS: m/z 1110.5 Th [C₇₂H₈₄N₇O₄]⁺

Example 45,10,15-tris-{[4-(N,N-dimethylpiperidin-4-ium)oxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide

ESI-MS: m/z 385.2 Th [C₇₅H₉₂N₇O₄]³⁺

Example 55,10,15-tris-[3-(2-morpholin-4-ylethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrin

ESI-MS: m/z 1158.8 Th [C₇₂H₈₄N₇O₇]⁺

Example 65,10,15-tris-{[3-(2-methylmorpholin-4-ium)ethoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide

ESI-MS: m/z 400.9 Th [C₇₅H₉₂N₇O₇]³⁺

Example 75,10,15-tris-{4-[4-(N,N-dimethylamino)phenoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrin

ESI-MS: m/z 1176.6 Th [C₇₈H₇₈N₇O₄]⁺

Example 85,10,15-tris-{4-[4-(N,N,N-trimethylammonium)phenoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide

ESI-MS: m/z 406.8 Th [C₈₁H₈₆N₇O₄]³⁺

Example 95,10,15-tris-{4-[3-(N,N-dimethylamino)phenyl]thiophenyl}-20-[(3-undecyloxy)phenyl]porphyrin

ESI-MS: m/z 1239.7 Th [C₇₉H₈₀N₇OS₃]⁺

Example 105,10,15-tris-{4-[3-(N,N,N-trimethylammonium)phenyl]thiophenyl}-20-[(4-undecyloxy)phenyl]porphyrintriiodide

ESI-MS: m/z 427.7 Th [C₈₂H₈₈N₇OS₃]³⁺

Example 115,10,15-tris-[3-(3-N,N-dimethylaminopropoxy)phenyl]-20-[(3-undecyloxy)phenyl]porphyrin

ESI-MS: m/z 1088.6 Th [C₇₀H₈₆N₇O₄]⁺

Example 125,10,15-tris-[3-(3-N,N,N-trimethylammoniumpropoxy)phenyl]-20-[(3-undecyloxy)phenyl]porphyrintriiodide

ESI-MS: m/z 377.7 Th [C₇₃H₉₄N₇O₄]³⁺

Example 135,10,15-tris-{4-[4-(N,N-dimethylamino)butoxy]phenyl]-20-[(4-undecyloxy)phenyl]porphyrin

ESI-MS: m/z 1131.6 Th [C₇₃H₉₂N₇O₄]⁺

Example 145,10,15-tris-{4-[4-(N,N,N-trimethylammonium)butoxy]phenyl}-20-[(4-undecyloxy)phenyl]porphyrintriiodide

ESI-MS: m/z 379.7 Th [C₇₆H₁₀₀N₇O₄]³⁺

Example 155-{4-{2,4,6-tris-[(dimethylamino)methyl]phenoxy}phenyl}-10,15,20-tris-[(4-decyloxy)phenyl]porphyrin

ESI-MS:: m/z 1346.9 Th [C₈₉H₁₁₆N₇O₄]⁺

Example 165-{4-{2,4,6-tris-[(trimethylammonium)methyl]phenoxy}phenyl}-10,15,20-tris-[(4-decyloxy)phenyl]porphyrintriiodide

ESI-MS: m/z 463.6 Th [C₉₂H₁₂₄N₇O₄]³⁺

Example 175-{3-[2-(dimethylamino)]-1-{[(dimethylamino)methyl]ethoxy}phenyl}-10,15,20-tris-[(3-decyloxy)phenyl]porphyrin

ESI-MS: m/z 1227.8 Th [C₈₁H₁₀₇N₆O₄]⁺

Example 185-{3-[2-(trimethylammonium)]-1-{[(trimethylammonium)methyl]ethoxy}phenyl}-10,15,20-tris-[(3-decyloxy)phenyl]porphyrindiiodide

ESI-MS: m/z 628.4 Th [C₈₃H₁₁₂N₆O₄]²⁺

Example 195,10,15-tris-{4-[3-(diethylamino)propoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrin

ESI-MS: m/z 1172.7 Th [C₇₆H₉₈N₇O₄]⁺

Example 205,10,15-tris-{4-[3-(trimethylammonium)propoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide

ESI-MS: m/z 419.6 Th [C₈₂H₁₁₂N₇O₄]³⁺

Example 215,10,15-tris-[4-(2-aminoethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrin

ESI-MS: m/z 962.5 Th [C₆₁H₆₈N₇O₄]⁺

Example 225,10,15-tris-{[4-(2-trimethylammonium)ethoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide

ESI-MS: m/z 363.5 Th [C₇₀H₈₈N₇O₄]³⁺

Example 235,10,15-tris-{{[4-(N,N,N-trimethylammonium)phenoxy]carbonyl}phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide

ESI-MS: m/z 434.6 Th [C₈₄H₈₆N₇O₇]³⁺

Example 245-{4-{{2-(trimethylammonium)-1-[(trimethylammonium)methyl]ethoxy}carbonyl}phenyl}-10,15,20-tris-[(3-decyloxy)phenyl]porphyrindiiodide

ESI-MS: m/z 1270.8 Th [C₈₃H₁₁₀N₆O₅]⁺

Example 25 Synthesis of5,15-bis-[3-(3-N,N,N-trimethylammoniumpropoxy)phenyl]porphyrin diiodideStep a) Synthesis of 2-(1H-pyrrol-2-ylmethyl)-1H-pyrrole(dipyrromethane)

To a solution of p-formaldehyde (1100 mg, 35 mmol) in pyrrole (50 ml,720 mmol), at 50° C., TFA (416 mg, 3.5 mmol) was added. The reactionmixture was kept under magnetic stirring, at room temperature, for 30minutes, then ethyl acetate was added and the solution washed withNaHCO₃ saturated solution, then the organic phase was dried on Na₂SO₄.After evaporation the crude product was purified by chromatography onsilica gel (Petroleum Ether/Ethyl acetate 4/1+1% TEA). 1950 mg (yield38%) of the product were obtained.

¹H NMR (300 MHz, DMSO-d⁶): 6.55 (2H, m), 5.85 (2H, m), 5.71 (2H, m),3.78 (2H, s).

¹³C NMR (75 MHz, CDCl₃): 129.0, 117.3, 108.3, 106.4, 26.2.

Step b) Synthesis of 3-(3-hydroxypropoxy)benzaldehyde

To a solution of 3-hydroxybenzaldehyde (366 mg, 3 mmol) in anhydrous DMF(7 ml), under nitrogen atmosphere, K₂CO₃ (829 mg, 6 mmol), and, after 10minutes, 3-bromo-1-propanol (500 mg, 3.6 mmol) were added. The mixturewas heated to reflux for 2 hours, then water was added and the productwas extracted with CH₂Cl₂. The organic layers were washed with water andwith NaCl saturated solution, dried on Na₂SO₄. After evaporation of thesolvent the crude product was purified by chromatography on silica gel(Petroleum ether/Ethyl acetate 2/1); 520 mg (yield 95%) of title productwere obtained.

¹H NMR (300 MHz, CDCl₃): 9.95 (1H, s), 7.43 (2H, m), 7.38 (1H, d, J=1.8Hz), 7.17 (1H, m), 4.17 (2H, t, J=6 Hz), 3.86 (2H, t, J=6 Hz), 2.06 (2H,tt, J=6 Hz, 6 Hz).

¹³C NMR (75 MHz, CDCl₃): 192.1, 159.3, 137.7, 130.1, 123.6, 121.8,112.8, 65.7, 60.0, 31.8.

Step c) Synthesis 5,15-bis-[3-(3-hydroxypropoxy)phenyl]porphyrin

To a solution of 2-(1H-pyrrol-2-ylmethyl)-1H-pyrrole (236 mg, 1.6 mmol)and 3-3-hydroxypropoxy)benzaldehyde (305 mg, 1.6 mmol) in dry CH₂Cl₂(160 ml), trifluoroacetic acid (114 mg, 1 mmol) was added and themixture was kept under magnetic stirring, at room temperature, undernitrogen atmosphere, for 4 hours. Then p-chloranil (492 mg, 2 mmol) wasadded and the final mixture stirred for additional 5 hours, then theorganic phase was washed with Na₂CO₃ saturated solution, dried on Na₂SO₄and the solvent removed by evaporation. The crude product was purifiedby chromatography on silica gel (CHCl₃/MeOH 97/3), to give 100 mg oftitle product (yield 20%).

¹H NMR (300 MHz, CDCl₃): 10.32 (2H, s), 9.39 (4H, d, J=4.2 Hz), 9.12(4H, d, J=4.2 Hz), 7.85 (4H, m), 7.69 (2H, dd, J=8.4 Hz, 7.5 Hz), 7.36(2H, dd, J=8.4 Hz, 2.0 Hz), 4.36 (4H, t, J=6.0 Hz), 3.96 (4H, t, J=6.0Hz), 2.16 (4H, tt, J=6.0 Hz, 6.0 Hz), −3.15 (2H, s).

¹³C NMR (75 MHz, CDCl₃): 157.3, 146.9, 145.2, 142.7, 131.6, 131.0,128.0, 127.8, 121.2, 118.7, 114.0, 105.2, 65.9, 60.5, 32.0.

Step d) Synthesis of5,15-bis-[3-(3-methylsulphonylpropoxy)phenyl]porphyrin

To a solution of 5,15-bis-[3-(3-hydroxypropoxy)phenyl]porphyrin (30 mg,0.049 mmol) in anhydrous CH₂Cl₂, under nitrogen atmosphere, at 0° C.,triethylamine (29 mg mg, 0.29 mmol) and methansulphonylchloride (17 mg,0.15 mmol) were added. The mixture was kept under magnetic stirring at0° C. for 3 hours, then washed with NaHCO₃ saturated solution and withwater. The organic phase was dried under Na₂SO₄ and the solvent removedby evaporation. The crude product was purified by chromatography onsilica gel (CHCl₃), to obtain 17 mg of the pure title product (yield45%).

¹H NMR (300 MHz, CDCl₃): 10.33 (2H, s), 9.40 (4H, d, J=4.8 Hz), 9.12(4H, d, J=4.8 Hz), 7.90 (2H, d, J=7.5 Hz), 7.82 (2H, s), 7.70 (2H, dd,J=8.4 Hz, 7.5 Hz), 7.35 (2H, d, J=8.4 Hz), 4.54 (4H, t, J=6.3 Hz), 4.32(4H, t, J=5.7 Hz), 3.02 (6H, s), 2.34 (4H, tt, J=6.3 Hz, 5.7 Hz), −3.14(2H, bs).

¹³C NMR (75 MHz, DMSO-d⁶): 157.8, 147.0, 145.5, 142.5, 133.3, 131.5,128.9, 128.4, 121.7, 119.0, 115.0, 106.4, 98.8, 68.1, 64.6, 37.2, 29.3.

ESI-MS: m/z 767.5 Th (C₄₀H₃₉N₄O₈S₂)⁺

Step e) Synthesis of5,15-bis-[3-(3-N,N-dimethylaminopropoxy))phenyl]porphyrin

To a solution of 5,15-bis-[3-(3-methylsulphonylpropoxy)phenyl]porphyrin(15 mg, 0.019 mmol) in anhydrous DMF (2 ml), under nitrogen atmosphere,K₂CO₃ (14 mg, 0.11 mmol), and, after 10 minutes, dimethylaminehydrochloride (8 mg, 0.11 mmol) were added. The mixture was heated at80° C. for 15 hours, then water was added and the product was extractedwith CH₂Cl₂. The organic layers were washed with water and with NaClsaturated solution, dried on Na₂SO₄. After evaporation the crude productwas purified by flash chromatography (THF to THF/DMF 9/1). After thechromatography, the product was washed with CHCl₃/Petroleum Ether 1/1and 10 mg (yield 80%) of pure title product were obtained.

¹H NMR (300 MHz, D₂O+HCl): 10.83 (2H, s), 9.40 (4H, m), 8.95 (4H, m),7.83 (4H, m), 7.74 (2H, m), 3.38 (4H, m), 3.30 (4H, m), 2.78 (12H, s),2.19 (4H, m).

¹³C NMR (75 MHz, D₂O+HCl, selected data): 157.7, 145.1, 142.4, 139.8,131.8, 130.6, 130.3, 129.7, 124.4, 112.1, 116.5, 106.9, 65.7, 55.6,43.0, 24.3.

ESI-MS: m/z 665.6 Th (C₄₂H₄₅N₆O₂)⁺

Step f) Synthesis of 5,15-bis-[3-(3-N,N,N-trimethylammonium)propoxyphenyl]porphyrin diiodide

To a solution of5,15-bis-[3-(3-N,N-dimethylaminopropoxy)phenyl]porphyrin (26 mg, 0.039mmol) in dry NMP (5 ml), iodomethane (110 mg, 0.78 mmol) was added. Thereaction mixture was kept under magnetic stirring, at room temperature,for 24 hours, then diethyl ether was added slowly until a precipitateappeared. The suspension was filtered and the solid crystallized fromMeOH/diethyl ether to give 26 mg of pure title product (yield 70%).

¹H NMR (300 MHz, DMSO-d⁶): 10.64 (2H, s), 9.66 (4H, d, J=4.6 Hz), 9.07(4H, d, J=4.6 Hz), 7.86 (4H, m), 7.80 (2H, dd, J=8.1 Hz, 7.0 Hz), 7.48(2H, d, J=7.0 Hz), 4.32 (4H, t, J=5.7 Hz), 3.58 (4H, m), 3.10 (18H, s),2.29 (4H, m), −3.29 (2H, s).

¹³C NMR (75 MHz, DMSO-d⁶, selected data): 157.5, 146.8, 145.3, 142.3,133.0, 131.2, 128.8, 121.6, 118.7, 114.8, 108.6, 106.2, 65.6, 63.6,52.8, 23.1.

UV-VIS (DMF): λ_(max) 670, 629, 575, 535, 500, 381, 256, 244.

ESI-MS: m/z 347.4 Th (C₄₄H₅₀N₆O₂)²⁺

According to the procedures described in Example 25 the followingporphyrins have been prepared:

Example 26 5,15-bis-[4-(2-piperidin-1-ylethoxy)phenyl]porphyrin

ESI-MS: m/z 717.4 Th (C₄₆H₄₉N₆O₂)⁺

Example 27 5,15-bis-[4-(2-N-methylpiperidin-1-iumethoxy)phenyl]porphyrindiiodide

ESI-MS: m/z 373.2 Th (C₄₈H₅₄N₆O₂)²⁺

Example 285,15-bis-[4-(3-N,N-dimethylaminopropoxy)phenyl]-10,20-bis-[(3-decyloxy)phenyl]porphyrin

ESI-MS: m/z 1129.7 Th (C₇₄H₉₃N₆O₄)⁺

Example 295,15-bis-[4-[3-N,N,N-trimethylammoniumpropoxy)phenyl]-10,20-bis-[(3-decyloxy)phenyl]porphyrindiiodide

ESI-MS: m/z 579.3 Th (C₇₆H₉₈N₆O₄)²⁺

Example 30 5,15-bis 4-{[2-N,N-dimethylamino)ethylthio]phenyl}porphyrin

ESI-MS: m/z 669.39 Th (C₄₀H₄₁N₆S₂)⁺

Example 315,15-bis-{4-[2-(N,N,N-trimethylammonium)ethylthio]phenyl}porphyrindiiodide

ESI-MS: m/z 349.4 Th (C₄₂H₄₆N₆S₂)²⁺

Example 325,15-bis-{4-{2-[3-(trimethylammonium)phenoxy]ethoxy}phenyl}porphyrindiiodide

ESI-MS: m/z 425.2 Th (C₅₄H₅₄N₆O₄)²⁺

Example 335,15-bis-{4-{2-[3-(N,N,N-trimethylammonium)phenyl]-2-oxoethyl}-10,20-bis-[(3-decyloxy)phenyl]porphyrindiiodide

ESI-MS: m/z 639.4 Th (C₈₆H₉₈N₆O₄)²⁺

Example 34 Synthesis of5,15-bis-[3-(3-N,N,N-trimethylammoniumpropoxy)phenyl]porphyrinatezinc(II) diiodide Step a) Synthesis of5,15-bis-[3-(3-hydroxypropoxy)phenyl]porphyrinate zinc(II)

To a solution of 5,15-bis-[3-(3-hydroxypropoxy)phenyl]porphyrin (100 mg,0.16 mmol) in CHCl₃/THF 1/1 (10 ml), zinc acetate (183 mg, 1 mmol) wasadded and the mixture was kept under magnetic stirring, at 40° C., undernitrogen for 4 hours. Then the solid was filtered through celite and theliquid phase was dried on Na₂SO₄, then the solvent removed byevaporation to obtain 110 mg of title product (yield 98%) that was usedin the following step without further purification.

¹H NMR (300 MHz, CDCl₃): 10.24 (2H, s), 9.35 (4H, d, J=4.5 Hz), 9.08(4H, d, J=4.5 Hz), 7.81 (2H, d, J=8.1 Hz), 7.63 (2H, s), 7.58 (2H, dd,J=8.1 Hz, 7.5 Hz), 7.12 (2H, d, J=7.5 Hz), 3.96 (4H, m), 3.25 (4H, m),1.66 (4H, m).

¹³C NMR (75 MHz, CDCl₃): 156.9, 149.9, 149.7, 144.0, 132.4, 131.7,127.9, 127.3, 121.0, 119.5, 113.7, 106.1, 65.9, 60.3, 31.7.

Step b) Synthesis of5,15-bis-[3-(3-methylsulphonylpropoxy)phenyl]porphyrinate zinc(II)

To a solution of 5,15-bis-[3-(3-hydroxypropoxy)phenyl]porphyrinate zinc(100 mg, 0.14 mmol) in anhydrous CH₂Cl₂, under nitrogen atmosphere, at0° C., triethylamine (43 mg mg, 0.42 mmol) and methansulphonylchloride(36 mg, 0.31 mmol) were added. The mixture was kept under magneticstirring at 0° C. for 2 hours, then washed with NaHCO₃ saturatedsolution and with water. The organic phase was dried on Na₂SO₄ and thesolvent removed by evaporation. The crude product was purified by flashchromatography on silica gel (CHCl₃/MeOH 99/1), to obtain 70 mg of thepure title product (yield 60%).

¹H NMR (300 MHz, CDCl₃): 10.33 (2H, s), 9.44 (4H, d, J=4.5 Hz), 9.17(4H, d, J=4.5 Hz), 7.89 (2H, d, J=7.8 Hz), 7.82 (2H, s), 7.69 (2H, dd,J=8.1 Hz, 7.8 Hz), 7.35 (2H, d, J=8.1 Hz), 4.53 (4H, t, J=6.0 Hz), 4.31(4H, t, J=6 Hz), 3.02 (6H, s), 2.33 (4H, tt, J=6.0 Hz, 6.0 Hz).

¹³C NMR (75 MHz, CDCl₃): 156.9, 149.9, 149.5, 144.0, 132.5, 131.8,128.0, 127.6, 121.0, 119.6, 113.8, 106.3, 66.8, 63.4, 37.2, 29.2.

APCI-MS: m/z 829.1 Th (C₄₀H₃₉N₄O₈S₂Zn)⁺

Step c) Synthesis of5,15-bis-[3-(3-N,N-dimethylaminopropoxy))phenyl]porphyrinate zinc(II)

To a solution of5,15-bis-[3-(3-methylsulphonylpropoxy)phenyl]porphyrinate zinc (15 mg,0.019 mmol) in anhydrous DMF (2 ml), under nitrogen atmosphere, K₂CO₃(14 mg, 0.11 mmol), and, after 10 minutes, dimethylamine hydrochloride(8 mg, 0.11 mmol) were added. The mixture was heated at 80° C. for 15hours, then water was added and the product was extracted with CH₂Cl₂.The organic layers were washed with water and with NaCl saturatedsolution, then dried on Na₂SO₄. After evaporation the crude product waspurified by chromatography (THF to THF/DMF 9/1). After thechromatography, the product was washed with CHCl₃/Petroleum Ether 1/1and 10 mg (yield 80%) of pure product of the title were obtained.

¹H NMR (300 MHz, D₂O+HCl): 11.16 (2H, s), 9.67 (4H, d, J=4.5 Hz), 9.17(4H, m), 8.05 (2H, d, J=9.0 Hz), 7.82 (2H, dd, J=9.0 Hz, 8.4 Hz), 7.51(2H, d, J=8.4 Hz), 4.32 (4H, m), 3.35 (4H, t. J=8.2 Hz), 2.82 (12H, s),2.23 (4H, m).

¹³C NMR (75 MHz, D₂O+HCl, selected data): 157.8, 145.5, 142.8, 140.1,131.9, 131.0, 129.6, 124.8, 121.5, 116.5, 107.1, 65.8, 55.7, 43.0, 24.3.

UV-VIS (DMF): λ_(max) 544, 406, 310, 255, 244.

APCI-MS: m/z 727.0 Th (C₄₂H₄₅N₆O₂Zn)⁺

Step d) Synthesis of5,15-bis-[3-(3-N,N,N-trimethylammoniumpropoxy)phenyl]porphyrinatezinc(II) diiodide

To a solution of5,15-bis-[3-(3-N,N-dimethylaminopropoxy)phenyl]porphyrinate zinc (64 mg,0.088 mmol) in dry NMP (5 ml), iodomethane (374 mg, 2.63 mmol) wasadded. The reaction mixture was kept under magnetic stirring, at roomtemperature, for 24 hours, then diethyl ether was added slowly until aprecipitate appeared. The suspension was filtered and the solidcrystallized from MeOH/diethyl ether to give 70 mg of pure title product(yield 80%).

¹H NMR (300 MHz, DMSO-d⁶): 10.35 (2H, s), 9.48 (4H, d, J=4.2 Hz), 8.98(4H, d, J=4.2 Hz), 7.79 (4H, m), 7.73 (2H, dd, J=9.3 Hz, 7.0 Hz), 7.42(2H, d, J=9.3 Hz), 4.31 (4H, t, J=6.0 Hz), 3.57 (4H, m), 3.10 (18H, s),2.48 (4H, m).

¹³C NMR (75 MHz, DMSO-d⁶, selected data): 157.3, 149.7, 149.6, 132.8,132.3, 128.3, 121.7, 119.2, 114.3, 106.8, 65.7, 63.7, 52.9, 23.4.

UV-VIS (DMF): λ_(max) 544, 408, 392, 312, 264.

ESI-MS: m/z 347.4 Th (C₄₄H₅₀N₆O₂Zn)²⁺

Example 35 Synthesis of5,15-bis-[4-(4-N,N,N-trimethylammoniumphenoxy)phenyl]porphyrin diiodideStep a) Synthesis of 4-(4-nitrophenoxy)benzaldehyde

To a solution of 4-hydroxybenzaldehyde (366 mg, 3 mmol) in anhydrous DMF(7 ml), under nitrogen atmosphere, K₂CO₃ (829 mg, 6 mmol), and, after 10minutes, 4-bromonitrobenzene (726 mg, 3.6 mmol) were added. The mixturewas heated to reflux for 3 hours, then water was added and the productwas extracted with CH₂Cl₂. The organic layers were washed with water andwith NaCl saturated solution and dried with Na₂SO₄. After evaporation ofthe solvent the crude product was purified by chromatography on silicagel (Petroleum ether/Ethyl acetate 5/1); 605 mg (yield 82%) of puretitle product were obtained.

¹H NMR (300 MHz, CDCl₃): 9.99 (1H, s), 8.27 (2H, m), 7.94 (2H, m), 7.20(2H, m), 7.14 (2H, m).

¹³C NMR (75 MHz, CDCl₃): 190.7, 161.5, 160.6, 133.2, 132.3, 126.3,119.9, 119.0.

Step c) Synthesis of 5,15-bis-[4-(4-nitrophenoxy)phenyl]porphyrin

To a solution of 2-(1H-pyrrol-2-ylmethyl)-1H-pyrrole (200 mg, 1.37 mmol)and 4-(4-nitrophenoxy)benzaldehyde (305 mg, 1.6 mmol) in dry CH₂Cl₂ (130ml), trifluoroacetic acid (114 mg, 1 mmol) was added and the mixture waskept under magnetic stirring, at room temperature, under nitrogenatmosphere for 3 hours, then p-chloranil (492 mg, 2 mmol) was added andthe final mixture stirred for additional 15 hours, then the organicphase was washed with Na₂CO₃ saturated solution, dried with Na₂SO₄ andthe solvent removed by evaporation. The crude product was purified bychromatography on silica gel (CHCl₃/Petroleum ether 3/1), to give 45 mgof title product (yield 10%).

¹H NMR (300 MHz, CDCl₃): 10.37 (2H, s), 9.45 (4H, d, J=4.5 Hz), 9.12(4H, d, J=4.5 Hz), 8.41 (4H, m), 8.34 (4H, m), 7.54 (4H, m), 7.41 (4H,m), −3.11 (2H, bs).

¹³C NMR (75 MHz, CDCl₃, selected data): 154.9, 147.1, 145.3, 140.1,138.4, 136.4, 132.0, 130.8, 128.6, 126.3, 126.2, 118.9, 117.7, 105.6.

UV-VIS (DMF): 8_(max) 629, 574, 535, 409, 395, 382, 305, 249, 233.

ESI-MS: m/z 737.3 Th (C₄₄H₂₉N₆O₆)⁺

Step d) Synthesis of 5,15-bis-[4-(4-aminophenoxy)phenyl]porphyrin

To a solution of 5,15-bis-[4-(4-nitrophenoxy)phenyl]porphyrin (70 mg,0.095 mmol) in CHCl₃ (10 ml), saturated with concentrated HCl,SnCl₂.2H₂O (105 mg, 0.475 mmol) was added and the mixture was kept undermagnetic stirring, at room temperature for 24 h, then cold water wasadded, the mixture was neutralized with a solution 15% of ammonia, andthe organic phase was extracted, dried on Na₂SO₄, then the solvent wasremoved by evaporation. The crude product was purified by chromatographyon silica gel (THF to THF/DMF 9/1), to give 43 mg of title product(yield 67%).

¹H NMR (300 MHz, CDCl₃): 10.31 (2H, s), 9.40 (4H, d, J=4.8 Hz), 9.12(4H, d, J=4.8 Hz), 8.16 (4H, m), 7.35 (4H, m), 7.21 (4H, m), 6.86 (4H,m), −3.10 (2H, s ¹³C NMR (75 MHz, CDCl₃, selected data): 159.1, 148.5,147.4, 145.1, 136.5, 135.9, 131.6, 131.0, 126.2, 121.7, 118.9, 117.7,116.4, 115.5, 105.2.

UV-VIS (DMF): λ_(max) 630, 576, 536, 501, 382, 265, 253.

ESI-MS: m/z 677.3 Th (C₄₄H₃₃N₆O₂)³⁰

Step f) Synthesis of5,15-bis-[(4-(4-N,N,N-trimethylammoniumphenoxy)phenyl]porphyrin diiodide

To a solution of 5,15-bis-[4-(4-aminophenoxy)phenyl]porphyrin (30 mg,0.042 mmol) in dry NMP (5 ml), iodomethane (150 mg, 1.1 mmol) was added.The reaction mixture was kept under magnetic stirring, at roomtemperature, for 24 hours, then diethyl ether was added slowly until aprecipitate appeared. The suspension was filtered and the solidcrystallized from MeOH/diethyl ether to give 35 mg of pure title product(yield 80%).

¹H NMR (300 MHz, DMSO-d⁶): 10.66 (2H, s), 9.71 (4H, d, J=4.8 Hz), 9.12(4H, d, J=4.8 Hz), 8.35 (4H, m), 8.14 (4H, m), 7.58 (8H, m), 3.68 (18H,m), −3.27 (2H, s).

¹³C NMR (75 MHz, DMSO-d⁶, selected data): 156.3, 147.1, 142.9, 136.8,133.2, 131.4, 123.3, 120.0, 118.5, 115.3, 111.2, 106.4, 98.6, 57.2.

UV-VIS (DMF): λ_(max) 577, 539, 502, 392, 265, 254, 244, 235.

ESI-MS: m/z 381.3 Th (C₅₀H₄₆N₆O₂)²⁺

According to the procedures described in Example 35 the followingporphyrins have been prepared:

Example 36 5,15-bis-[3-(4-N,N-dimethylaminophenoxy)phenyl]porphyrin

ESI-MS: m/z 733.3 Th (C₄₈H₄₁N₆O₂)⁺

Example 375,15-bis-[3-(4-N,N,N-trimethylammoniumphenoxy)phenyl]porphyrin diiodide

ESI-MS: m/z 381.2 Th (C₅₀H₄₆N₆O₂)²⁺

Example 38 5,15-bis-[3-(4-N,N-dimethylaminophenyl)thiophenyl]porphyrin

ESI-MS: m/z 765.3 Th (C₄₈H₄₁N₆S₂)⁺

Example 395,15-bis-[3-(4-N,N,N-trimethylammoniumthiophenoxy)phenyl]porphyrindiiodide

ESI-MS: m/z 795.3 Th (C₄₈H₄₁N₆O₂)²⁺

Example 405,15-bis-4-[3-(N,N-dimethylaminophenoxy)phenyl]-10,20-bis-[(4-decyloxy)phenyl]porphyrin

ESI-MS: m/z 1197.6 Th (C₈₀H₈₉N₆O₄)²⁺

Example 415,15-bis-4-[3-(N,N,N-trimethylammoniumphenoxy)phenyl]-10,20-bis-[(4-decyloxy)phenyl]porphyrindiiodide

ESI-MS: m/z 795.3 Th (C₈₂H₉₄N₆O₄)²⁺

According with the procedure reported in Examples 1 and 34 or bymetallation of metal free porphyrins, the following Zn(II)-porphyrinateshave been prepared:

Example 425,10,15-tris-{4-[4-(N,N-dimethylamino)butoxy]phenyl}-20-[(4-undecyloxy)phenyl]porphyrinatezinc(II)

ESI-MS: m/z 1194.9 Th [C₇₃H₉₀N₇O₄Zn]⁺

Example 435,10,15-tris-{4-[4-(N,N,N-trimethylammonium)butoxy]phenyl}-20-[(4-undecyloxy)phenyl]porphyrinatezinc(II) triiodide

ESI-MS: m/z 418.3 Th [C₇₇H₁₀₂N₇O₄Zn]³⁺

Example 44 5,15-bis-[4-(2-piperidin-1-ylethoxy)phenyl]porphyrinatezinc(II)

ESI-MS: m/z 780.3 Th (C₄₆H₄₇N₆O₂Zn)⁺

Example 455,15-bis-[4-(2-N-methylpiperidin-1-iumethoxy)phenyl]porphyrinatezinc(II) diiodide

ESI-MS: m/z 405.2 Th (C₄₈H₅₂N₆O₂Zn)²⁺

1. Compounds of general formula (I)

wherein R is the following group of formula (II)

wherein X is selected from the group consisting of O, S, CH₂, COO,CH₂CO, O(CH₂)₂O, O(CH₂)₃O and N; Z is selected from between N and CH₂N;Y is selected from aliphatic groups, linear or branched, saturated orunsaturated, having from 1 to 10 carbon atoms, and phenyl, or Y formswith Z a saturated or unsaturated heterocycle, selected from the groupconsisting of: morpholine, piperidine, pyrimidine, piperazine,pyrrolidine, pyrroline, aniline, julolidine(2,3,6,7-tetrahydro-1H,5H-pirido[3,2,1-Ij]quinoline, and substitutedforms thereof; R₄ and R₅, equal or different from each other, areselected from H and alkyl groups having from 1 to 3 carbon atoms, orthey form with the Z group a saturated or unsaturated heterocycle,selected from the group consisting of: morpholine, piperidine,pyrimidine, piperazine, pyrrolidine, pyrroline, aniline, julolidine(2,3,6,7-tetrahydro-1H,5H-pirido[3,2,1-Ij]quinoline), and substitutedforms thereof; R₆ is selected from H and aliphatic groups, linear orbranched, saturated or unsaturated, having from 1 to 5 carbon atoms,comprising a saturated heterocycle selected from the group consistingof: morpholine, piperidine, piperazine, pyrrolidine, and substitutedforms thereof; d, m, and n, equal of different from each other, areselected from 0 and 1; v and s, equal or different from each other, areintegers comprised between 1 and 3; R₁ is selected from H and a group offormula (III)

wherein G is selected from H and P— (CH₂)₁—(W)_(f)-J, wherein P isselected from the group consisting of O, CH₂, CO₂, NHCONH and CONH; l isan integer comprised between 0 and 5; W is selected from the groupconsisting of O, CO₂, CONH and NHCONH; f is selected from between 0 and1; J is H or an alkyl group (CH₂)_(q)—CH₃, wherein q is an integercomprised between 0 and 20; R₂ and R₃, equal or different from eachother, are selected from between R and R₁, wherein R and R₁ are definedas above, M is chosen from 2H and a metal selected from the groupconsisting of Zn, Mg, Pt, Pd, Si(OR₇)₂, Ge(OR₇)₂ and AlOR₇, wherein R₇is chosen from between H and C1-C15 alkyl, and pharmaceuticallyacceptable salts thereof, with the exception of the following compounds:a) compound of formula (I) wherein M is 2H, R₁═R₃═H, R═R₂ is a group offormula (II) in which s is 1, X is O, Y is (CH₂)₃, v is 1, Z is N,n=d=l, m is 0, and R₄═R₅═H; and b) compound of formula (I) wherein M is2H, R₁═R₃═H, R═R₂ is a group of formula (II) in which s is 1, X is O, Yis (CH₂)₃, v is 1, Z is N, n=d=1, m is 0, R₄ and R₅ form with Z aphthalimido group.
 2. Compounds of general formula (I) according toclaim 1, in which the group R comprises at least one substituent bearingtertiary or quaternary nitrogen.
 3. Compounds of general formula (I)according to claim 1, wherein the group

is selected from the group consisting of:


4. Compounds of general formula (I) according to claim 1, wherein R₆ isselected from aliphatic groups, linear or branched, saturated orunsaturated, having from 1 to 5 carbon atoms, substituted withalkylamine or alkylammonium groups having alkyl chains comprising from 1to 5 carbon atoms.
 5. Compounds of general formula (I)

wherein R is the following group of formula (II)

wherein X is selected from the group consisting of O, S, CH₂, COO,CH₂CO, O(CH₂)₂O, O(CH₂)₃O and N; Z is selected from between N and CH₂N;Y is selected from aliphatic groups, linear or branched, saturated orunsaturated, having from 1 to 10 carbon atoms, and phenyl or Y formswith Z a pyridine or substituted pyridine heterocycle; R₄ and R₅, equalor different from each other, are selected from H and alkyl groupshaving from 1 to 3 carbon atoms, or they form with the Z group apyridine or substituted pyridine heterocycle; R₆ is selected from H andaliphatic groups, linear or branched, saturated or unsaturated, havingfrom 1 to 5 carbon atoms, or comprising a saturated heterocycle selectedfrom the group consisting of: morpholine, piperidine, piperazine,pyrrolidine, and substituted forms thereof; d, m, and n, equal ofdifferent from each other, are selected from 0 and 1; v and s, equal ordifferent from each other, are integers comprised between 1 and 3; R₁ isselected from H and a group of formula (III)

wherein G is selected from H and P— (CH₂)₁— (W)_(f)-J, wherein P isselected from the group consisting of O, CH₂, CO₂, NHCONH and CONH; l isan integer comprised between 0 and 5; W is selected from the groupconsisting of O, CO₂, CONH and NHCONH; f is selected from between 0 and1; J is H or an alkyl group (CH₂)_(q)—CH₃, wherein q is an integercomprised between 0 and 20; R₂ and R₃, equal or different from eachother, are selected from between R and R₁, wherein R and R₁ are definedas above, M is chosen from 2H and a metal selected from the groupconsisting of Zn, Mg, Pt, Pd, Si(OR₇)₂, Ge(OR₇)₂ and AlOR₇, wherein R₇is chosen from between H and C1-C15 alkyl, and pharmaceuticallyacceptable salts thereof, with the exception of the following compounds:a) compound of formula (I) wherein M is 2H, R₁═R₃═H, R═R₂ is a group offormula (II) in which s is I, X is O, Y is (CH₂)₃, v is 1, Z is N,n=d=1, m is 0, and R₄═R₅═H; and b) compound of formula (I) wherein M is2H, R₁═R₃═H, R═R₂ is a group of formula (II) in which s is I, X is O, Yis (CH₂)₃, v is I, Z is N, n=d=1, m is O, R₄ and R₅ form with Z aphthalimido group.
 6. Compounds of general formula (I) according toclaim 5, wherein the group

is selected from the group consisting of:


7. Compounds of general formula (I)

wherein R is the following group of formula (II)

wherein X is selected from the group consisting of O, S, CH₂, COO,CH₂CO, O(CH₂)₂O, O(CH₂)₃O and N; wherein the group

is selected from the group consisting of:

v and s, equal or different from each other, are integers comprisedbetween 1 and 3; R₁ is selected from H and a group of formula (III)

wherein G is selected from H and P—(CH₂)₁—(W)_(f)— J, wherein P isselected from the group consisting of O, CH₂, CO₂, NHCONH and CONH; l isan integer comprised between 0 and 5; W is selected from the groupconsisting of O, CO₂, CONH and NHCONH; f is selected from between 0 and1; J is H or an alkyl group (CH₂)_(q)—CH₃, wherein q is an integercomprised between 0 and 20; R₂ and R₃, equal or different from eachother, are selected from between R and R₁, wherein R and R₁ are definedas above, M is chosen from 2H and a metal selected from the groupconsisting of Zn, Mg, Pt, Pd, Si(OR₇)₂, Ge(OR₇)₂ and AlOR₇, wherein R₇is chosen from between H and C1-C15 alkyl, and pharmaceuticallyacceptable salts thereof.
 8. Compounds of general formula (I) accordingto claim 1, selected from the group consisting of:5,10,15-tris-[4-(2-N,N,N-trimethylammoniumethoxy)-phenyl]-20-[(4-decyloxy)-phenyl]porphyrintriiodide,5,10,15-tris-[4-(2-N,N,N-trimethylammoniumethoxy)-phenyl]-20-[(4-decyloxy)-phenyl]porphyrinatezinc (II) triiodide,5,10,15-tris-[4-(2-N,N-dimethylaminoethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrin],5,10,15-tris-[4-(2-N,N-dimethylaminoethoxy)-phenyl]-20-[(4-decyloxy)phenyl]porphyrinatezinc (II),5,10,15-tris-{[4-(N-methylpiperidin-4-yl)oxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrin,5,10,15-tris-{[4-(N,N-dimethylpiperidin-4-ium)oxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide,5,10,15-tris-[3-(2-morpholin-4-ylethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrin,5,10,15-tris-{[3-(2-methylmorpholin-4-ium)ethoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide,5,10,15-tris-{4-[4-(N,N-dimethylamino)phenoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrin,5,10,15-tris-{4-[4-(N,N,N-trimethylammonium)phenoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide,5,10,15-tris-{4-[3-(N,N-dimethylamino)phenyl]thiophenyl}-20-[(3-undecyloxy)phenyl]porphyrin,5,10,15-tris-{4-[3-(N,N,N-trimethylammonium)phenyl]thiophenyl}-20-[(4-undecyloxy)phenyl]porphyrintriiodide,5,10,15-tris-[3-(3-N,N-dimethylaminopropoxy)phenyl]-20-[(3-undecyloxy)phenyl]porphyrin,5,10,15-tris-[3-(3-N,N,N-trimethylammoniumpropoxy)phenyl]-20-[(3-undecyloxy)phenyl]porphyrintriiodide,5,10,15-tris-{4-[4-(N,N-dimethylamino)butoxy]phenyl}-20-[(4-undecyloxy)phenyl]porphyrin,5,10,15-tris-{4-[4-(N,N,N-trimethylammonium)butoxy]phenyl}-20-[(4-undecyloxy)phenyl]porphyrintriiodide,5-{4-{2,4,6-tris-[(dimethylamino)methyl]phenoxy}phenyl}-10,15,20-tris-[(4-decyloxy)phenyl]porphyrin,5-{4-{2,4,6-tris-[(trimethylammonium)methyl]phenoxy}phenyl}-10,15,20-tris-[(4-decyloxy)phenyl]porphyrintriiodide,5-{3-[2-(dimethylamino)]-1-{[(dimethylamino)methyl]ethoxy}phenyl}-10,15,20-tris-[(3-decyloxy)phenyl]porphyrin,5-{3-[2-(trimethylammonium)]-1-{[(trimethylammonium)methyl]ethoxy}phenyl}-10,15,20-tris-[(3-decyloxy)phenyl]porphyrindiiodide,5,10,15-tris-{4-[3-(diethylamino)propoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrin,5,10,15-tris-{4-[3-(trimethylammonium)propoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide,5,10,15-tris-[4-(2-aminoethoxy)phenyl]-20-[(4-decyloxy)phenyl]porphyrin,5,10,15-tris-{[4-(2-trimethylammonium)ethoxy]phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide,5,10,15-tris-{{[4-(N,N,N-trimethylammonium)phenoxy]carbonyl}phenyl}-20-[(4-decyloxy)phenyl]porphyrintriiodide,5-{4-{{2-(trimethylammonium)-1-[(trimethylammonium)methyl]ethoxy}carbonyl}phenyl}-10,15,20-tris-[(3-decyloxy)phenyl]porphyrindiiodide, 5,15-bis-[3-(3-N,N,N-trimethylammoniumpropoxy)phenyl]porphyrindiiodide, 5,15-bis-[4-(2-piperidin-1-ylethoxy)phenyl]porphyrin,5,15-bis-[4-(2-N-methylpiperidin-1-iumethoxy)phenyl]porphyrin diiodide,5,15-bis-[4-(3-N,N-dimethylaminopropoxy)phenyl]-10,20-bis-[(3-decyloxy)phenyl]porphyrin,5,15-bis-[4-[3-N,N,N-trimethylammoniumpropoxy)phenyl]-10,20-bis-[(3-decyloxy)phenyl]porphyrindiiodide, 5,15-bis 4-{[2-(N,N-dimethylamino)ethylthio]phenyl}porphyrin,5,15-bis-{4-[2-(N,N,N-trimethylammonium)ethylthio]phenyl}porphyrindiiodide,5,15-bis-{4-{2-[3-(trimethylammonium)phenoxy]ethoxy}phenyl}porphyrindiiodide,5,15-bis-{4-[2-[3-(N,N,N-trimethylammonium)phenyl]-2-oxoethyl}-10,20-bis-[(3-decyloxy)phenyl]porphyrindiiodide,5,15-bis-[3-(3-N,N,N-trimethylammoniumpropoxy)phenyl]porphyrinatezinc(II) diiodide,5,15-bis-[3-(3-N,N-dimethylaminopropoxy)phenyl]porphyrinate zinc(II),5,15-bis-[4-(4-N,N,N-trimethylammoniumphenoxy)phenyl]porphyrin diiodide,5,15-bis-[4-(4-aminophenoxy)phenyl]porphyrin,5,15-bis-[3-(4-N,N-dimethylaminophenoxy)phenyl]porphyrin,5,15-bis-[3-(4-N,N,N-trimethylammoniumphenoxy)phenyl]porphyrindiiiodide, 5,15-bis-[3-(4-N,N-dimethylaminophenyl)thiophenyl]porphyrin,5,15-bis-[3-(4-N,N,N-trimethylammoniumthiophenoxy)phenyl]porphyrindiiiodide,5,15-bis-4-[3-(N,N-dimethylaminophenoxy)phenyl]-10,20-bis-[(4-decyloxy)phenyl]porphyrin,5,15-bis-4-[3-(N,N,N-trimethylammoniumphenoxy)phenyl]-10,20-bis-[(4-decyloxy)phenyl]porphyrindiiodide,5,10,15-tris-{4-[4-(N,N-dimethylamino)butoxy]phenyl]-20-[(4-undecyloxy)phenyl]porphyrinatezinc(II),5,10,15-tris-{4-[4-(N,N,N-trimethylammonium)butoxy]phenyl}-20-[(4-undecyloxy)phenyl]porphyrinatezinc(II) triiodide,5,15-bis-[4-(2-piperidin-1-ylethoxy)phenyl]porphyrinate zinc(II), and5,15-bis-[4-(2-N-methylpiperidin-1-iumethoxy)phenyl]porphyrinatezinc(II) diiodide.
 9. Pharmaceutical compositions comprising as theactive principle at least a compound of general formula (I) as definedin claim 1 in combination with pharmaceutically acceptable excipientsand/or diluents.
 10. A method of sterilizing wounds, comprisingadministering to a patient in need of such a treatment an effectiveamount of at least a compound of general formula (I) as defined in claim1, and thereafter irradiating the patient with light of appropriatewavelength.